Rational Design of Mn-Based Metal-Organic Framework Mn-Cip for Chemodynamic Therapy-Chemotherapy and Tumor Metastasis Suppression.

Single cancer treatment was inadequate to meet the expected therapeutic requirements. Multimodal therapy leveraged the synergistic effects of diverse therapeutic modalities and had emerged as a promising antitumor strategy. Meanwhile, certain substances with antimicrobial activity were capable of exerting inhibitory effects on tumor metastasis. In this work, a manganese-based metal-organic framework Mn-Cip, which exhibited prominent chemodynamic therapeutic efficacy and inhibition of tumor metastasis, was designed and synthesized. To enhance therapeutic effects, the anticancer drug methotrexate (MTX) was loaded into Mn-Cip to construct MTX@Mn-Cip integrating chemodynamic therapy (CDT), chemotherapy, and tumor metastasis suppression. In a simulated tumor microenvironment, the system released anticancer drug MTX to realize chemotherapy while delivering manganese ions to initiate Fenton-like reactions and facilitate ·OH generation, thereby enabling chemodynamic therapy (CDT). Moreover, in vitro cell scratch assay and transwell cell invasion assay revealed that MTX@Mn-Cip could remarkably inhibit the migration and invasion of 4T1 cells, thus exerting potent tumor metastasis suppression effects. In vitro assays demonstrated excellent biocompatibility with mouse fibroblast cells (L929 cells) and significant suppression of viability in mouse breast cancer cells (4T1 cells). MTX@Mn-Cip provides an effective strategy for achieving an ideal cancer therapeutic regimen through the synergistic effects of chemotherapy, CDT, and tumor metastasis suppression.